Neurofilament Light Protein Rod Domain Exhibits Structural Heterogeneity.
Biomolecules
; 14(1)2024 Jan 09.
Article
en En
| MEDLINE
| ID: mdl-38254685
ABSTRACT
Neurofilaments are neuron-specific proteins that belong to the intermediate filament (IFs) protein family, with the neurofilament light chain protein (NFL) being the most abundant. The IFs structure typically includes a central coiled-coil rod domain comprised of coils 1A, 1B, and 2, separated by linker regions. The thermal stability of the IF molecule plays a crucial role in its ability for self-association. In the current study, we investigated the thermal stability of NFL coiled-coil domains by analyzing a set of recombinant domains and their fusions (NFL1B, NFL1A+1B, NFL2, NFL1B+2, and NFLROD) via circular dichroism spectroscopy and differential scanning calorimetry. The thermal stability of coiled-coil domains is evident in a wide range of temperatures, and thermal transition values (Tm) correspond well between isolated coiled-coil domains and full-length NFL. NFL1B has a Tm of 39.4 °C, and its' fusions, NFL1A+1B and NFL1B+2, have a Tm of 41.9 °C and 41.5 °C, respectively. However, in the case of NFL2, thermal denaturation includes at least two thermal transitions at 37.2 °C and 62.7 °C. These data indicate that the continuous α-helical structure of the coil 2 domain has parts with varied thermal stability. Among all the NFL fragments, only NFL2 underwent irreversible heat-induced denaturation. Together, these results unveil the origin of full-length NFL's thermal transitions, and reveal its domains structure and properties.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Asunto principal:
Filamentos Intermedios
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Miembro 14 de la Superfamilia de Ligandos de Factores de Necrosis Tumoral
Idioma:
En
Revista:
Biomolecules
Año:
2024
Tipo del documento:
Article
País de afiliación:
Rusia